J 2024

Global interactome mapping reveals pro-tumorigenic interactions of NF-κB in breast cancer

LAPČÍK, Petr; R. Greg STACEY; David POTĚŠIL; Petr KULHÁNEK; Leonard J. FOSTER et. al.

Basic information

Original name

Global interactome mapping reveals pro-tumorigenic interactions of NF-κB in breast cancer

Authors

LAPČÍK, Petr; R. Greg STACEY; David POTĚŠIL; Petr KULHÁNEK; Leonard J. FOSTER and Pavel BOUCHAL

Edition

Molecular and Cellular Proteomics, Elsevier, 2024, 1535-9484

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

Netherlands

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

http://dx.doi.org/10.1016/j.mcpro.2024.100744

UT WoS

001347387500001

EID Scopus

2-s2.0-85191897708

Keywords in English

NF-κB; RELA; Proteomics; Protein complexes; Interaction; Breast cancer; Protein correlation profiling; AlphaPullDown

Links

LX22NPO5102, research and development project. NU22-08-00230, research and development project. CIISB III, large research infrastructures. e-INFRA CZ II, large research infrastructures.
Changed: 25/3/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

NF-κB pathway is involved in inflammation, however, recent data shows its role also in cancer development and progression, including metastasis. To understand the role of NF-κB interactome dynamics in cancer, we study the complexity of breast cancer interactome in luminal A breast cancer model and its rearrangement associated with NF-κB modulation. Liquid chromatography-mass spectrometry measurement of 160 size exclusion chromatography (SEC) fractions identifies 5460 protein groups. 7568 interactions among these proteins have been reconstructed by PrInCE algorithm, of which 2564 have been validated in independent datasets. NF-κB modulation leads to rearrangement of protein complexes involved in NF-κB signaling and immune response, cell cycle regulation and DNA replication. Central NF-κB transcription regulator RELA co-elutes with interactors of NF-κB activator PRMT5, and these complexes are confirmed by AlphaPulldown prediction. A complementary immunoprecipitation experiment recapitulates RELA interactions with other NF-κB factors, associating NF-κB inhibition with lower binding of NF-κB activators to RELA. This study describes a network of pro-tumorigenic protein interactions and their rearrangement upon NF-κB inhibition with potential therapeutic implications in tumors with high NF-κB activity.
Displayed: 19/7/2025 23:07